Structural investigations of protein-lipid complexes using neutron scattering

Luke A Clifton, Stephen C L Hall, Najet Mahmoudi, Timothy J Knowles, Frank Heinrich, Jeremy H Lakey

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Neutron scattering has significant benefits for examining the structure of protein–lipid complexes. Cold (slow) neutrons are nondamaging and predominantly interact with the atomic nucleus, meaning that neutron beams can penetrate deeply into samples, which allows for flexibility in the design of samples studied. Most importantly, there is a strong difference in neutron scattering length (i.e., scattering power) between protium (H11, 99.98% natural abundance) and deuterium (H12 or D, 0.015%). Through the mixing of H 2O and D 2O in the samples and in some cases the deuterium labeling of the biomolecules, components within a complex can be hidden or enhanced in the scattering signal. This enables both the overall structure and the relative distribution of components within a complex to be resolved. Lipid–protein complexes are most commonly studied using neutron reflectometry (NR) and small angle neutron scattering (SANS). In this review the methodologies to produce and examine a variety of model biological membrane systems using SANS and NR are detailed. These systems include supported lipid bilayers derived from vesicle dispersions or Langmuir–Blodgett deposition, tethered bilayer systems, membrane protein–lipid complexes and polymer wrapped lipid nanodiscs. The three key stages of any SANS/NR study on model membrane systems—sample preparation, data collection, and analysis—are described together with some background on the techniques themselves.

Original languageEnglish
Pages (from-to)201-251
Number of pages51
JournalMethods in molecular biology
Publication statusE-pub ahead of print - 20 Jun 2019


  • Bilayer deposition
  • Deuteration
  • Isotopic contrast variation
  • Nanodiscs
  • Neutron reflectometry
  • Neutron scattering
  • Protein–lipid complexes
  • SMALPs
  • Small-angle neutron scattering
  • Supported lipid bilayers
  • Tethered lipid bilayer membranes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics


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